Chemistry Letters Vol.33, No.9 (2004)
1147
Table 2. Deprotection of N-protected TBDMS ethers of amino
alcohols
(1992).
4
5
6
R. F. Newton, D. P. Reynolds, M. A. W. Finch, D. R. Kelly,
and S. M. Roberts, Tetrahedron Lett., 20, 3981 (1979).
R. Baker, W. J. Cummings, J. F. Hayes, and A. Kumar,
J. Chem. Soc., Chem. Commun., 1986, 1237.
E. J. Thomas and A. C. Williams, J. Chem. Soc., Chem.
Commun., 1987, 992.
b
Entry
Substrate
Producta
Time/h
1.5
Yield/%
H
N
H
N
OTBDMS
Fmoc
OH
1
Fmoc
90
Ph
Ph
7
8
F. Franke and R. D. Guthrie, Aust. J. Chem., 31, 1285 (1978).
D. R. Kelly, S. M. Roberts, and R. F. Newton, Synth.
Commun., 9, 295 (1979).
H
N
H
N
2
OTBDMS
OTBDMS
OH
OH
1.5
92
Cbz
Cbz
Cbz
Cbz
9
1
G. Just and R. Zamboni, Can. J. Chem., 31, 1285 (1994).
0 E. A. Schmittling and J. S. Sawyer, Tetrahedron Lett., 32,
Ph
Ph
7
207 (1991).
11 C. Prkash, S. Saleh, and I. A. Blair, Tetrahedron Lett., 35,
565 (1994).
2 N. S. Wilson and B. A. Keay, Tetrahedron Lett., 38, 187
1997).
13 Z. Y. Jiang and Y. G. Wang, Tetrahedron Lett., 44, 3859
2003).
H
N
H
N
3
4
1.5
1.5
95
93
7
CH Ph
CH Ph
2
2
1
(
H
N
H
N
OH
Boc
OTBDMS Boc
CH Ph
(
CH Ph
2
2
1
4 R. D. Crouch, M. Stieff, J. L. Frie, A. B. Cadwallader, and
D. C. Bevis, Tetrahedron Lett., 40, 3133 (1999).
a
All the products were characterized by IR, NMR, and MS.
Isolated Yields.
b
15 B. E. Blass, C. L. Harris, and D. E. Portlock, Tetrahedron
Lett., 42, 1611 (2001).
the acid sensitive ketal group (entry 16). The phenolic TBDMS
ether required 20 h and 1 equiv. of KHSO4 for complete depro-
tection. Thus in the presence of phenolic TBDMS ether, benzylic
ether was cleaved selectively (entry 13).
We next extended our methodology to the deprotection
of N-protected TBDMS ethers of amino alcohols (Table 2).
The deprotection proceeds smoothly in 1.5 h without affecting
the amino protective groups in excellent yields.
16 A. V. Ankala and G. Genteany, Tetrahedron Lett., 38, 4729
(2002).
17 A. D. Gupta, R. Singh, and V. K. Singh, Synlett, 1996, 69.
18 M. Wang, C. Li, D. Yin, and X. T. Liang, Tetrahedron Lett.,
32, 7207 (1991).
19 G. Sabitha, M. Syamala, and J. S. Yadav, Org. Lett., 1, 1701
(1999).
20 R. Nagarajan and P. T. Perumal, Chem. Lett., 33, 288 (2004).
21 R. S. Kumar, R. Nagarajan, and P. T. Perumal, Synthesis,
2004, 949.
We thank the Council of Scientific and Industrial Research,
New Delhi, India for financial support.
2
2 General experimental procedure: To a stirred solution of
TBDMS ether (1 mmol) in 3 mL of 30% aq. methanol added
0.4 mmol of KHSO4 and stirred at room temperature. The
progress of the reaction was monitered by TLC. After the
disappearance of starting material, methanol was removed,
added 5 mL of water and extracted with 20 mL (2 Â 10) of
ethyl acetate. The organic layer was dried over anhydrous so-
dium sulfate and solvent was removed under reduced pres-
sure. The crude product was purified by column chromatog-
raphy. The alcohol obtained was identical with authentic
sample by TLC, IR, NMR, and Mass.
References and Notes
1
T. W. Greene and P. G. M. Wuts, ‘‘Protective Groups in
Organic Synthesis,’’ 2nd ed., John Wiley & Sons, New York
(
1999), p 17.
E. J. Corey and A. Venkateswarlu, J. Am. Chem. Soc., 94,
190 (1992).
a) T. Toshima, K. Tatsuta, and M. Kinoshita, Bull. Chem
Soc. Jpn., 61, 2369 (1988). b) F. Franke and R. D. Guthrie,
Aust. J. Chem., 31, 1285 (1978). c) L. A. Paquette, A. M.
Doherty, and C. M. Rayner, J. Am. Chem. Soc., 114, 3910
2
3
6
Published on the web (Advance View) August 7, 2004; DOI 10.1246/cl.2004.1146